A disease specific structure termed scrapie associated fibril (SAF) has been observed by negative stain electron microscopy exclusively in the uncoventional slow virus diseases. SAF have been seen in naturally occurring or experimentally induced cases of Creutzfeldt-Jakob disease, Kuru, Scrapie, Gerstmann-Straussler syndrome and chronic wasting disease. These structures have not been found in a comprehensive series of controls sharing common histopathologies, ultrastructural features and disease symptoms. Evidence suggests SAF to be a component of the infectious agent or the agent itself. Purification of scrapie infectivity in the 263K hamster model has yielded SAF as the only ultrastructural entity; an indication of identity between agent and SAF. A scrapie agent strain specific polypeptide has been observed by polyacrylamide gel electrophoresis in purified preparations of SAF; 2lK for l39A scrapie agent, 22K for ME7 scrapie agent and 25K for 263K scrapie agent. The implication of these findings is that the scrapie agent imparts genetic control over the components of SAF by way of its own genetic information. The purification and molecular characterization of SAF represents a means to link scrapie infectivity with a morphologically identifiable structure, a unique polypeptide and potentially with a nucleic acid. Antibody probes and potential nucleic acid probes generated to SAF will permit studies on the replication and pathogenesis of these agents and provide a much needed diagnostic tool within the area of unconventional slow virus diseases. These probes provide the potential to investigate the role of similar agents in Senile Dementia of the Alzheimer Type and in other CNS disorders of unknown etiology.